Thyroid Physiology

Negative Bio-feedback loop

  1. Physiology of the thyroid and the production of thyroid hormones
    1. Iodine ion (I-) is trapped through an aerobic process via active transport into the thyroid follicles. This starts the process of producing certain thyroid hormones
      1. Injection of pertechnetate causes competitive inhibition of iodine concentration in the thyroid (99mTcO4- and I- compete for the available binding sites on the thyroid follicles)
      2. Salivary glands, gastric mucosa, small intestine, mammary glands, skin, and hair trap iodine to a lesser degree (but it isn't organified)
      3. Trapped iodine concentrations in the thyroid are between 25mg (normal) to as high as 5000mg (hyper) times that of the surrounding tissue
      4. Cells of the thyroid are seen at this link
    1. The follicular cells in the thyroid organifi the iodine by peroxidases in the presence of hydrogen peroxide converting I- to I2
      1. Organic binding occurs on tyrosyl residue
      1. Tyrosyl is located on thyrogobulin (TBG) and forms monoiodotyrosine globulin (MIT)
      2. This occurs within the follicular spaces and forms the following:
        1. MIT + MIT = Diiodotyrosine. (DIT)
        1. MIT + DIT = Triiodothyronine (T3)
        2. DIT + DIT = Tetraiodothyronine - Thyroxine (T4 )
      3. T3 and T4 are bound to TBG and TBG circulates in the blood stream
        1.   All T4 is produced in the thyroid
        2. Only 20% of T3 is produced by the thyroid, while the remainder is produced peripherally via monodeiodination, breaking down of T4
        3.   It is T3 that becomes the active ingredient that directly affects the metabolism of the body at the cellular level (not T4)
      4. Storage and released
        1. Thyroid hormones are stored on TBG in colloid form
        2. TSH stimulates the release of TBG and T4 from colloid within the follicular cells
        3. Hydrolysis of intracellular TBG releases T3 and T4 into circulation
        4. Note - it is the free form of T3 that is active. In the bound form it is considered inactive
        5. Note - DIT, MIT and TBG are also released into circulation
      5. In a normal thyroid, T3 and T4 levels are affected by Thyrotropin-Releasing Hormone (TRH) and Thyroid Stimulating Hormone (TSH) production
        1. Excess levels of T3 and T4 cause reduced production of TRH and TSH
        2. Decreased levels T3 and T4 cause increased levels of TRH and TSH
        3. Since T3 and T4 cause an opposite reaction the term negative biofeedback loop is used
        4. Reduced levels of TRH and TSH reduces iodine trapping, resulting in reduced production of T3and T4
        5. Increased levels of TRH and TSH increase iodine trapping, resulting increased production of T3 and T4
        6. Hence, the effects of TSH and TRH reverse the T3 and T4 production
        7. Refer to the diagram above to identify the process being discussed
      6. Hypothalamus produces TRH
      7. Anterior Pituitary produces TSH
      8. A caveat or two - TBG levels will increase when the thyroid is radiated or in the presence of thyroid cancer
        1. Following radioiodine ablation, TBG levels initially increase, then decrease over time
        2. However, following a thryoid oblation, when TBG levels sudden increase this is an indication of recurring thyroid cancer
      9. Process of deiodination (breaking down T4 ) usually occurs in peripheral tissue
        1. Bound T4 becomes free and circulates in peripheral tissue
        2. (T4 T1/2 is ~7 days in circulation as it deiodinates
        3. About 70% deiodinates to T3 or rT3
        4. T3 (T1/2 = 1 day) and rT3 is known as reverse T3
        5. The active form used by the body is T3
        6. rT3 is inactive and plays no role in the body's metabolism - want to know more about rT3?
        7. Deiodination occurs in the liver, kidneys, brain and pituitary via an enzyme 5'-deiodinase
          1. Reduction of this enzyme reduces deiodination, which results in lower levels of T3 being produced and causes increased levels of rT3
          2. Type I disorder occurs in the liver and kidneys (causing reduced levels of T3)
          3. Type II disorder occurs in the pituitary (causing reduced levels of T3)

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